Department of Endocrinology and Metabolism, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang 832002, PR China.
Mol Med Rep. 2012 Feb;5(2):457-61. doi: 10.3892/mmr.2011.660. Epub 2011 Nov 2.
p53 and PTEN are the two most frequently mutated tumor suppressors in human cancer. However, literature on the effect of the joint inactivation of tumor-suppressor genes in soft tissue sarcoma (STS) is lacking. The purpose of this study was to investigate whether p53 and PTEN mutations play a role in the carcinogenesis of STS, as well as to evaluate their mutual role in STS pathogenesis. We screened mutations of p53 and PTEN in 86 human STSs using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing, respectively. p53 mutations were detected in 25.6% (22 out of 86) of STSs: 6 cases of p53 mutations were detected in 46 cases of specific reciprocal translocations in STSs (13.0%), 16 cases were detected in 40 cases of nonspecific reciprocal translocations in STSs (40.0%); the majority of the mutations were point mutations in exon 6-7. Furthermore, PTEN mutations were observed in 2 out of 86 STSs (2.3%). Two out of 86 cases revealed a 130th codon G>A missense mutation in exon 8 of PTEN which resulted in an Arg change to Gln in the PTEN protein structure; and a 334th codon A>T missense mutation in exon 8 of PTEN, which resulted in an Asn change to Lys in the PTEN protein structure. All subjects were examined for p53 exon 5-9 mutations and for PTEN exon 5-9 mutations. However, no tumors contained an alteration of the two genes. The findings indicate that p53 mutations may be involved in the oncogenesis of STS and also suggest that p53 may function as a potential molecular marker for distinguishing between STSs with specific reciprocal translocations and nonspecific reciprocal translocations. Although the existence of PTEN mutations in STS was detected, the PTEN mutation frequency was quite low. We conclude that PTEN may have played a less prognostic role than p53 in the development and malignant transformation of STS in the patients examined.
p53 和 PTEN 是人类癌症中最常发生突变的两种肿瘤抑制基因。然而，关于软组织肉瘤（STS）中联合失活肿瘤抑制基因的文献尚缺乏。本研究旨在探讨 p53 和 PTEN 突变是否在 STS 的发生发展中起作用，并评估它们在 STS 发病机制中的相互作用。我们应用聚合酶链反应-单链构象多态性（PCR-SSCP）和 DNA 测序分别筛选 86 例 STS 中 p53 和 PTEN 的突变。在 86 例 STS 中检测到 p53 突变 25.6%（22/86）：46 例 STS 特异性相互易位中发现 6 例 p53 突变（13.0%），40 例 STS 非特异性相互易位中发现 16 例 p53 突变（40.0%）；突变主要位于外显子 6-7。此外，在 86 例 STS 中发现 2 例 PTEN 突变（2.3%）：PTEN 外显子 8 的第 130 密码子 G>A 错义突变导致第 49 位精氨酸变为谷氨酰胺，PTEN 外显子 8 的第 334 密码子 A>T 错义突变导致第 111 位天冬酰胺变为赖氨酸。所有病例均检测了 p53 外显子 5-9 和 PTEN 外显子 5-9 的突变，但没有肿瘤同时存在两种基因的改变。研究结果提示 p53 突变可能参与 STS 的发生发展，并且 p53 可能作为区分 STS 特异性相互易位和非特异性相互易位的潜在分子标志物。尽管在 STS 中检测到了 PTEN 突变，但 PTEN 突变频率相当低。我们的结论是，在研究的 STS 患者中，PTEN 可能比 p53 对 STS 的发展和恶性转化发挥的预后作用更小。
